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Review
. 2025 Sep 1;71(9):691-700.
doi: 10.1097/MAT.0000000000002512. Epub 2025 Jul 17.

Dosing Reliability of Direct Thrombin Inhibitors in Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis

Patrick M Wieruszewski  1   2 , Hannah M Brinkman  2 , Jamel P Ortoleva  3 , Juan G Ripoll  1 , Sarah E Pieterick  4 , Katharine E Damico  5 , Subhasis Chatterjee  6   7 , Erica D Wittwer  1 , Danielle J Gerberi  8 , Jacopo D'Andria Ursoleo  9 , Erin D Wieruszewski  2   10 , Troy G Seelhammer  1
Affiliations
Review

Dosing Reliability of Direct Thrombin Inhibitors in Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis

Patrick M Wieruszewski et al. ASAIO J. .

Abstract

Empirical evidence suggests direct thrombin inhibitors (DTIs) produce more favorable hemostatic outcomes than heparin in patients supported by extracorporeal membrane oxygenation (ECMO), yet the exact mechanisms responsible are unknown. We systematically searched databases and registers for studies comparing DTIs to heparin in humans receiving ECMO. A total of 28 studies were identified, most of which (n = 25) used bivalirudin, while the rest (n = 3) used argatroban. In random-effects meta-analysis, DTIs achieved the therapeutic anticoagulation range faster (mean difference = -6.96 hours, 95% confidence interval [CI] = -11.98 to -1.95, p = 0.006) and maintained the therapeutic range for a greater proportion of time (mean difference = 18.6%, 95% CI = 8.78-28.42, p < 0.001) than heparin. Subgroup analysis revealed these effects were similarly significant in adult patients and when bivalirudin was the DTI; however, they were not significant in pediatric patients or when argatroban was the DTI. Sensitivity analysis confirmed robustness of the primary findings in only low-risk of bias studies and in only studies published as full papers. In summary, DTIs-specifically bivalirudin-were associated with faster time to therapeutic anticoagulation and maintained the goal range for a greater percentage of time than heparin during ECMO support.

Keywords: ECLS; ECMO; anticoagulation; argatroban; bivalirudin; direct thrombin inhibitors; heparin; mechanical circulatory support.

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Conflict of interest statement

Disclosure: P.M.W. serves as a consultant for Wolters Kluwer/UpToDate and has previously served as a consultant for Viatris Inc. E.D.W. has previously served as a consultant for Pacira Biosciences. The other authors have no conflicts of interest to report.

References

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